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Purity: ≥98%
PNU-159682 (PNU) is a highly potent metabolite of the anthracycline nemorubicin (MMDX) with excellent cytotoxicity. PNU-159682 was remarkably more cytotoxic than MMDX and doxorubicin in vitro, and was effective in the two in vivo tumor models tested, i.e., disseminated murine L1210 leukemia and MX-1 human mammary carcinoma xenografts.
| Targets |
Daunorubicins/Doxorubicins
Topoisomerase I |
|---|---|
| ln Vitro |
A sulforhodamine B assay demonstrates the cytotoxic effects of PNU-159682 (0-500 nM; exposed to the compounds for 1 hour and then cultured in compound-free medium for 72 hours). This was observed in human tumor cell lines. For the cells HT-29, A2780, DU145, EM-2, Jurkat, and CEM, the IC70 values are 0.577 nM, 0.39 nM, 0.128 nM, and 0.081 nM, 0.086 nM, and 0.075 nM, respectively[1]. It works against human tumor cell lines, with IC70 values for MMDX and doxorubicin ranging from 68 nM to 578 nM and 181 nM to 1717 nM, respectively[1]. MMAE is not as effective against NHL cell lines as PNU-159682. In an assay for cell viability, PNU-159682 is antagonistic to BJAB. Luc, WSU-DLCL2, SuDHL4.Luc, Granta-519, and Luc, with corresponding IC50 values of 0.10 nM, 0.020 nM, 0.055 nM, and 0.1 nM. However, MMAE opposes BJAB. Luc, WSU-DLCL2, Granta-519, SuDHL4.Luc, and 0.54 nM, 0.25 nM, 1.19 nM, and 0.25 nM, in that order[2].
PNU-159682 has the potential to create a new class of ADCs and is thousands of times more cytotoxic than doxorubicin. In vitro, PNU159682?to?anti-CD22?antibody (anti-CD22-NMS249) demonstrates potent anti-tumor properties. In vitro viability assays of NHL cell lines, anti-CD22-NMS249 (PNU159682-to-anti-CD22 antibody) is active and 2–20 times more potent than pinatuzumab vedotin; the ADC anti-CD22-NMS249 is against BJAB. The IC50 values of Luc, Granta-519, SuDHL4.Luc, and WSU-DLCL2 are 0.058 nM, 0.030 nM, 0.0221 nM, and 0.01 nM, in that order[3]. The activity of PNU-159682 (100 μM) to inhibit topoisomerase II unknotting is weak. With an IC50 of 25 nM, PNU-159682 exhibits a cytotoxic effect on SKRC-52 cells that express CAIX[4]. |
| ln Vivo |
In the murine L1210 leukemia model, PNU-159682 (single-dose; intravenous; 15 μg/kg) is the maximum tolerated dose. PNU-159682 exhibits enhanced in vivo antitumor activity. PNU-159682's antitumor effect (life span increase of 29%) is similar to that of 90 μg/kg MMDX (life span increase of 36%)[1].
In MX-1 human mammary carcinoma mice, PNU-159682 (i.v. 4 μg/kg; q7dx3; 40 days) exhibits a therapeutic response. Furthermore, four of the seven mice given PNU-159682 show total tumor regression starting on day 39[1]. PNU-159682 can be used to create a new class of ADCs because it is more cytotoxic than doxorubicin. In vivo, PNU159682?to?anti-CD22?antibody (anti-CD22-NMS249) demonstrates potent anti-tumor properties. Mice respond well to the ADC dose (anti-CD22-NMS249; 50 μg/m2 conjugated PNU-159682), which causes less than 10% weight loss[2]. Anti-CD22-NMS249 (single dose; 2 mg/kg) has comparable efficacy to anti-CD22-vc-MMAE in the BJAB.Luc model. AntiCD22-NMS249, at a dose of 2 mg/kg, completely eradicates the tumors (NMS249: 110-134%TGI vs. vc-MMAE: 114-143%TGI). Furthermore, a single 2 mg/kg dose of antiCD22-NMS249 causes three weeks of tumor stasis[1]. |
| Cell Assay |
Cell Line: Jurkat, CEM, HT-29, A2780, DU145, and EM-2 cells
Concentration: 0-500 nM Incubation Time: cultivated in compound-free medium for 72 hours after being exposed to PNU-159682 for one hour. Result: was more potent than doxorubicin by 6,420 to 2,100 fold and MMDX by 2,360 to 790 fold, respectively. PNU-159682's displayed IC70 values are in the subnanomolar range (0.07-0.58 nM) and significantly less than those found for doxorubicin and MMDX. |
| Animal Protocol |
Animal Model: MX-1 tumor fragments in four- to six-week-old female CD-1 athymic nude mice[1]
Dosage: 4 μg/kg Administration: Intravenous injection; q7dx3; 40 days Result: demonstrated anti-cancer properties in human mammary carcinoma xenografts (MX-1) treated with PNU-159682. |
| References |
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| Molecular Formula |
C32H35NO13
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|---|---|
| Molecular Weight |
641.6192
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| CAS # |
202350-68-3
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| Related CAS # |
PNU-159682;202350-68-3
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| SMILES |
C[C@H]1[C@@H]2[C@H](C[C@@H](O1)O[C@H]3C[C@@](CC4=C3C(=C5C(=C4O)C(=O)C6=C(C5=O)C(=CC=C6)OC)O)(C(=O)CO)O)N7CCO[C@@H]([C@H]7O2)OC
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| InChi Key |
SLURUCSFDHKXFR-WWMWMSKMSA-N
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| InChi Code |
InChI=1S/C32H35NO13/c1-13-29-16(33-7-8-43-31(42-3)30(33)46-29)9-20(44-13)45-18-11-32(40,19(35)12-34)10-15-22(18)28(39)24-23(26(15)37)25(36)14-5-4-6-17(41-2)21(14)27(24)38/h4-6,13,16,18,20,29-31,34,37,39-40H,7-12H2,1-3H3/t13-,16-,18-,20-,29+,30+,31-,32-/m0/s1
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| Chemical Name |
(7S,9S)-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-7-(((1S,3R,4aS,9S,9aR,10aS)-9-methoxy-1-methyloctahydro-1H-pyrano[4',3':4,5]oxazolo[2,3-c][1,4]oxazin-3-yl)oxy)-7,9,10,12-tetrahydrotetracen-5(8H)-one
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| Synonyms |
PNU-159682; PNU 159682; PNU159682
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~155.86 mM）
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| Solubility (In Vivo) |
10% DMSO+ 40% PEG300+ 5% Tween-80+ 45% saline: ≥ 2.5 mg/mL (3.90 mM) (Please use freshly prepared in vivo formulations for optimal results.)
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5586 mL | 7.7928 mL | 15.5855 mL | |
| 5 mM | 0.3117 mL | 1.5586 mL | 3.1171 mL | |
| 10 mM | 0.1559 mL | 0.7793 mL | 1.5586 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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